Field of the Invention
This application relates to methods for automated assessment of celiac disease; and more particularly to algorithm processes implemented by a computer to assess gross tissue morphometry for the purpose of diagnosing celiac disease and monitoring treatment efficacy.
Description of the Related Art
Celiac disease is an inflammatory disease that impacts the gastrointestinal (GI) track of patients [Catassi C, Fasano A, Am J Med, 2010; 123(8):691-693]. The inflammatory response is initiated by a reaction to gliadin in gluten, and clinical symptoms can be variable. Celiac disease can present as constipation, depression, fatigue, osteoporosis, acid reflux, infertility, as dermatologic conditions, and other less common symptoms.
Roughly 1% of the United States' population has celiac disease and the prevalence in Western Europe can be as high as 2.4% [Rubio-Tapia A, Ludvigsson J F, Am J Gastroenterol, 2010; 107:1538-1544]. Often the majority of patients do not know that they have celiac disease [Rubio-Tapia A, Ludvigsson J F, Am J Gastroenterol, 2010; 107:1538-1544]. The average time to diagnosis can be years, and patients are typically diagnosed when they meet four of the five following criteria: 1) typical clinical symptoms of celiac disease, 2) positive serologic markers such as serum anti-transglutaminase (TTG) antibodies or anti-gliadin antibodies, 3) small intestinal biopsy showing absent or blunted villi and increased numbers of intraepithelial cells, 4) positive genetic screening for HLA-DQ2 or -DQ8, and 5) improvement of symptoms on a gluten-free diet [Catassi C, Fasano A, Am J Med, 2010; 123(8):691-693].
Histologic scoring of small intestine biopsies remain the ‘gold standard’ for diagnosing celiac disease in patients suspected to have the disease. The histology scoring paradigm is based on the Marsh-Oberhuber classification which integrates measurements of intraepithelial lymphocytes, crypt hyperplasia, and villous atrophy [Oberhuber G et al., Eur J Gasteroenterol Hepatol, 1999; 11 (10):1185-1194].
Like most histologic scoring paradigms, the Marsh-Oberhuber classification is a semi-quantitative scoring scheme. Specifically, the assessment of villus atrophy in human tissues is a qualitative process that is dependent on the subjective assessment of tissue by an experienced pathologist. Risdon and Keeling have described a semi-quantitative method for assessing tissue sections [Risdon R A and Keeling J W, Gut, 1974; 15:9-18]. However, this method remains a manual assessment of tissue that is both subjective and time consuming.